Caveolin-1 sensitizes rat pituitary adenoma GH3 cells to bromocriptine induced apoptosis.
Caveolin-1 sensitizes rat pituitary adenoma GH3 cells to bromocriptine induced apoptosis.
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DOI：
10.1186/1475-2867-7-1
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发表时间：
2007-03-02
影响因子：
5.8
通讯作者：
Ju YT
中科院分区：
文献类型：
--
作者：
Jiang YN;Li YH;Ke MW;Tseng TY;Tang YB;Huang MC;Cheng WT;Ju YT
催乳素瘤是人类最常见的脑垂体瘤。多巴胺D2受体激动剂溴隐亭已广泛应用于临床，分别通过抑制高催乳素血症和诱导肿瘤细胞凋亡来治疗人乳腺肿瘤和催乳素瘤，但溴隐亭诱导垂体瘤细胞凋亡的分子机制尚不清楚。Caveolin-1是一种膜锚定蛋白，富含小凹，即信号转导分子集中在质膜上的倒置烧瓶状内陷。目前，小窝蛋白-1被认为是细胞增殖的负性调节因子，通过阻断细胞表膜受体和细胞内信号蛋白级联的信号转导而促进细胞凋亡。大鼠垂体腺瘤GH3细胞表达内源性小窝蛋白-1，暴露于溴隐亭后，细胞凋亡率增加，萎缩。因此，GH3细胞系是研究溴隐亭对催乳素瘤分子作用的理想模型。经溴隐亭处理后，GH3细胞内源性小窝蛋白-1的表达增加。瞬时表达的小鼠重组小窝蛋白1通过增强caspase8活性诱导GH3细胞凋亡。溴隐亭对小窝蛋白1诱导GH3细胞凋亡有明显的增敏作用。溴隐亭处理后，小窝蛋白-1在酪氨酸14位的磷酸化增强，提示溴隐亭诱导的小窝蛋白-1的磷酸化可能参与了对溴隐亭敏感的GH3细胞的凋亡。我们的结果表明，小窝蛋白-1增加了对垂体腺瘤GH3细胞诱导凋亡的敏感性，并可能有助于临床溴隐亭治疗后肿瘤的缩小。
Prolactinoma is the most frequent pituitary tumor in humans. The dopamine D2 receptor agonist bromocriptine has been widely used clinically to treat human breast tumor and prolactinoma through inhibition of hyperprolactinemia and induction of tumor cell apoptosis, respectively, but the molecular mechanism of bromocriptine induction of pituitary tumor apoptosis remains unclear. Caveolin-1 is a membrane-anchored protein enriched on caveolae, inverted flask-shaped invaginations on plasma membranes where signal transduction molecules are concentrated. Currently, caveolin-1 is thought to be a negative regulator of cellular proliferation and an enhancer of apoptosis by blocking signal transduction between cell surface membrane receptors and intracellular signaling protein cascades. Rat pituitary adenoma GH3 cells, which express endogenous caveolin-1, exhibit increased apoptosis and shrinkage after exposure to bromocriptine. Hence, the GH3 cell line is an ideal model for studying the molecular action of bromocriptine on prolactinoma. The expression of endogenous caveolin-1 in GH3 cells was elevated after bromocriptine treatment. Transiently expressed mouse recombinant caveolin-1 induced apoptosis in GH3 cells by enhancing the activity of caspase 8. Significantly, caveolin-1 induction of GH3 cell apoptosis was sensitized by the administration of bromocriptine. Phosphorylation of caveolin-1 at tyrosine 14 was enhanced after bromocriptine treatment, suggesting that bromocriptine-induced phosphorylation of caveolin-1 may contribute to sensitization of apoptosis in GH3 cells exposed to bromocriptine. Our results reveal that caveolin-1 increases sensitivity for apoptosis induction in pituitary adenoma GH3 cells and may contribute to tumor shrinkage after clinical bromocriptine treatment.
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影响因子：
8
作者：
Lee, SW;Reimer, CL;Schnitzer, JE
通讯作者：
Schnitzer, JE
DOI：
10.1152/ajplung.00293.2003
发表时间：
2004-07-01
影响因子：
4.9
作者：
Ono, K;Iwanaga, Y;Hasegawa, K
通讯作者：
Hasegawa, K
影响因子：
3.3
作者：
Singh, RD;Puri, V;Pagano, RE
通讯作者：
Pagano, RE
影响因子：
3.4
作者：
Navakauskiene, R;Treigyte, G;Magnusson, KE
通讯作者：
Magnusson, KE
影响因子：
4.8
作者：
Krump, E;Nikitas, K;Grinstein, S
通讯作者：
Grinstein, S